Graves' Disease is characterised by an overactive thyroid gland, which results in the production of an excessive amount of thyroid hormone and enlargement of the thyroid gland (goitre). The resulting state of hyperthyroidism may cause a wide range of neuropsychological and physical symptoms. GD is the most common cause of hyperthyroidism (60-90% of all cases) and usually presents itself during midlife, but also appears in children, adolescents, and the elderly. It affects up to 2% of the female population, and is between five and ten times as common in females as in males. Pediatric GD affects about 6,000 children in the US and 6,000 in the EU. GD is also the most common cause of severe hyperthyroidism, which is accompanied by more clinical signs and symptoms and laboratory abnormalities as compared with milder forms of hyperthyroidism.
There is a strong hereditary component linked to GD. There are no recent population studies on GD, however, a few quasi population studies on hyperthyroidism do exist and all estimates for incidence and prevalence of GD are thus approximate. The incidence of hyperthyroidism varies from 26:100,000 to 93:100,000 and the overall prevalence is estimated to be at 1.3%, with 42% of cases being overt and 62% subclinical.
About 30-50% of people with GD will also suffer from Graves' opthalmopathy (GO), a protrusion of one or both of the eyes. Many cases of GO are mild and self-limiting, however 20% of cases have significant/moderate to severe disease, with at least half of these require steroids and 3-5% of GO patients have painful, sight-threatening disease with dysthyroid optic neuropathy (DON). The budging of the eyes may cause severe dryness of the cornea as the eye lids are unable to close at night. Increased pressure in the optic nerve can lead to visual field defects and vision loss. GO may also be associated with pretibial myxedemia.
The symptoms and signs of GD virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being GO, goitre, and pretibial myxedema. Symptoms of hyperthyroidism may include insomnia, hand tremor, hyperactivity, hair loss, excessive sweating, heat intolerance and weight loss despite increased appetite. Further signs are most commonly a diffusely enlarged (usually symmetric) non-tender thyroid, lid lag, excessive lacrimation due to Graves' opthalmopathy, arrhythmias of the heart and hypertension. Thyrotoxic patients may experience behavioural and personality changes, such as psychosis, agitation, and depression. In milder hyperthyroidism, patients may experience less overt manifestations, for example anxiety, restlessness, irritability and emotional lability.
There is currently no cure available for GD and present treatments are therefore directed towards targeting the presenting symptoms. There are three treatment modalities for GD, oral antithyroid drugs (ATDs), radioactive iodine (RAI) and thyroidectomy. The latter two approaches result in lifetime supplementation of thyroid hormones. Therapy with radioiodine is the most common treatment in the United States, whilst ATDs are the first line treatment in Europe, Japan and most of the rest of the world.
ATD therapy is associated with some rare side-effects and has a remission rate of 50-60%. There is growing recognition the RAI can precipitate or worsen active GO and the number of patients treated with ATDs is the United States is increasing.
Due to the varying success of each treatment option, patients are often subjected to more than one approach if the first attempted treatment does not prove entirely successful. The risk of relapse or subsequent hypothyroidism is substantial and the general efficacy of available treatments for GD is less than desired. There is thus a need for alternative therapies for GD that are effective at treating GD and at alleviating or reducing the symptoms of the disease.